Oral squamous cell carcinoma cells modulate osteoclast function by RANKL-dependent and -independent mechanisms.
Oral squamous cell carcinoma (SCC) cells frequently invade mandibular bone, and bone invasion is a common clinical problem. Recent studies have revealed that bone resorption by osteoclasts is an important step in the progress of bone invasion by oral SCCs. We previously reported that oral SCC cells induce osteoclastogenesis by suppressing osteoprotegerin (OPG) in host cells. In the present study, we examined the effects of oral SCCs on osteoclast function. Both BHY cells, a human oral SCC cell line, and its conditioned medium (BHY-CM) stimulated osteoclast survival by suppressing Bim, a pro-apoptotic protein, depending on extracellular signal-regulated kinase (ERK) and multinucleation. Adding BHY cells but not BHY-CM induced pit-forming activity by osteoclasts and adding OPG abrogated the activity. Thus, oral SCC cells regulate not only osteoclastogenesis but also its function.
Tada
Takeyuki
T
Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Fukuoka 814-0193, Japan.
Shin
Masashi
M
Fukushima
Hidefumi
H
Okabe
Koji
K
Ozeki
Satoru
S
Okamoto
Masato
M
Jimi
Eijiro
E
D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D053244:Osteoprotegerin / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D053244:Osteoprotegerin; D011518:Proto-Oncogene Proteins; D053245:RANK Ligand; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3